Subhan Fazli, Kang Hae Yeong, Lim Yeseon, Ikram Muhammad, Baek Sun-Yong, Jin Songwan, Jeong Young Hun, Kwak Jong Young, Yoon Sik
Department of Anatomy, Pusan National University School of Medicine, Yangsan, Gyeongsangnam-do 50612, Republic of Korea.
Pioneer Research Center, Suwon 16499, Republic of Korea.
Oxid Med Cell Longev. 2017;2017:9703609. doi: 10.1155/2017/9703609. Epub 2017 Jun 22.
Skin diseases associated with inflammation or oxidative stress represent the most common problem in dermatology. The present study demonstrates that fish scale collagen peptides (FSCP) protect against CoCl-induced cytotoxicity and TNF--induced inflammatory responses in human HaCaT keratinocyte cells. Our study is the first to report that FSCP increase cell viability and ameliorate oxidative injury in HaCaT cells through mechanisms mediated by the downregulation of key proinflammatory cytokines, namely, TNF-, IL-1, IL-8, and iNOS. FSCP also prevent cell apoptosis by repressing Bax expression, caspase-3 activity, and cytochrome c release and by upregulating Bcl-2 protein levels in CoCl- or TNF--stimulated HaCaT cells. In addition, the inhibitory effects of FSCP on cytotoxicity and the induction of proinflammatory cytokine expression were found to be associated with suppression of the ROS, MAPK (p38/MAPK, ERK, and JNK), and NF-B signaling pathways. Taken together, our data suggest that FSCP are useful as immunomodulatory agents in inflammatory or immune-mediated skin diseases. Furthermore, our results provide new insights into the potential therapeutic use of FSCP in the prevention and treatment of various oxidative- or inflammatory stress-related inflammation and injuries.
与炎症或氧化应激相关的皮肤病是皮肤科最常见的问题。本研究表明,鱼鳞胶原蛋白肽(FSCP)可保护人HaCaT角质形成细胞免受CoCl诱导的细胞毒性和TNF-α诱导的炎症反应。我们的研究首次报道,FSCP通过下调关键促炎细胞因子TNF-α、IL-1、IL-8和诱导型一氧化氮合酶(iNOS)介导的机制,提高HaCaT细胞的活力并减轻氧化损伤。FSCP还通过抑制CoCl或TNF-α刺激的HaCaT细胞中Bax表达、caspase-3活性和细胞色素c释放,并上调Bcl-2蛋白水平来防止细胞凋亡。此外,发现FSCP对细胞毒性和促炎细胞因子表达诱导的抑制作用与抑制活性氧(ROS)、丝裂原活化蛋白激酶(p38/MAPK、ERK和JNK)以及核因子κB(NF-κB)信号通路有关。综上所述,我们的数据表明FSCP可作为炎症或免疫介导性皮肤病的免疫调节剂。此外,我们的结果为FSCP在预防和治疗各种氧化或炎症应激相关的炎症和损伤方面的潜在治疗用途提供了新的见解。